Deciphering the molecular circuitry that controls cell cycle progression in bacteria

破译控制细菌细胞周期进程的分子电路

• 批准号: 10249364
• 负责人: Paola E Mera
• 金额: $ 29.3万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-05 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249364
• 关键词: Address; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Model; Binding; Biological Models; Carbon; Caulobacter crescentus; Cell Cycle; Cell Cycle Progression; Cell Cycle Regulation; Cell Size; Cell Survival; Cell division; Cell physiology; Cells; Centromere; Chromosome Segregation; Chromosomes; Complex; Cytokinesis; DNA biosynthesis; Data; Defect; Dependence; Development; Drug Targeting; Event; Genetic; Genetic Transcription; Goals; Health; Link; Maintenance; Metabolic; Metabolism; Modeling; Molecular; Molecular Target; Nutrient; Outcome; Process; Protein Dynamics; Proteins; Proteomics; Publishing; Regulation; Regulation of Cell Size; Replication Initiation; Resistance; Role; Testing; Variant; base; cell type; chromosome replication; design; event cycle; genome integrity; insight; novel; prevent; segregation; temporal measurement; transcriptomics; z-ring

Maintaining the integrity of the genome is essential to cell survival. To accomplish this vital task, major cell cycle events including chromosome replication, segregation, and proper timing of cytokinesis are exquisitely coordinated, temporally and spatially. Any defect that disturbs this coordination can be lethal. Although replication, segregation, and cell division have been extensively studied in bacteria, our understanding of how these processes are coordinated remains limited. Bacteria’s survival also depends on their ability to coordinate cell cycle progression with environmental fluctuations. In this project, we focus on the conserved chromosome replication initiator protein DnaA and its non-replicative functions. The long-term goal is to characterize the molecular functions of regulators that coordinate the progression of the cell cycle and thus represent potential drug targets. The overall objective of this project is to define the mechanisms used to temporally coordinate the onset of chromosome replication with the progression of the cell cycle using the bacterial model system Caulobacter crescentus. The central hypothesis is that DnaA controls the activity of key regulators involved in chromosome segregation and cell size determination. The focus of Aim 1 is to define how DnaA coordinates chromosome replication with the onset of segregation by characterizing the physical association of DnaA with the chromosomal locus the centromere over the cell cycle. The focus of Aim 2 is to define the molecular network that links DnaA’s activity to cell size regulation and its dependency on nutrient availability. Information garnered from this project will provide valuable insights into strategies used by bacteria to temporally and spatially coordinate the multiple mechanisms that are fundamental for the cell survival.

维持基因组的完整性对于细胞存活至关重要。为了完成这项重要的任务，主要单元格 周期事件，包括染色体复制，隔离和细胞因子的适当时机 临时和空间协调。打扰这种协调的任何缺陷都可能致命。虽然 复制，隔离和细胞分裂已经广泛研究了细菌，我们对如何理解 这些过程是协调的。细菌的生存也取决于它们的能力 与环境波动协调细胞周期的进程。在这个项目中，我们专注于配置 染色体复制引发剂蛋白DNAA及其非复制功能。长期目标是 表征调节剂的分子功能，以协调细胞周期的进展，从而 代表潜在的药物靶标。该项目的总体目的是定义用于 暂时协调染色体复制的发作与使用该细胞周期的进展 细菌模型系统花椰菜新月形。中心假设是DNAA控制 参与染色体分离和细胞尺寸确定的关键调节剂。目标的重点是 定义DNAA如何通过表征染色体复制与隔离开始 DNAA与染色体基因座的物理缔合在整个细胞周期内。重点 AIM 2是定义将DNAA活性与细胞大小调节及其依赖性联系起来的分子网络 关于营养的可用性。从该项目中获得的信息将为策略提供宝贵的见解 细菌用于临时和空间协调多种机制 细胞存活。